Preparation of a quaternary ammonium hydroxide and use thereof for the preparation of a quaternary ammonium salt

Abstract

The invention relates to a process for the preparation of a quaternary ammonium hydroxide, in particular denatonium hydroxide, and the use thereof for the preparation of a quaternary ammonium salt, in particular of denatonium benzoate or a denatonium fatty acid derivative. Due to its extremely bitter taste, this latter compound is applied in the art as an aversive agent, biocide, antifoulant and flavorant. It is usually prepared from a quaternary ammonium halide in an organic environment, which after isolation and purification is converted to a hygroscopic and unstable hydroxide intermediate, which in turn is immediately converted to the salt of interest in the solvent in which it is prepared. It is now found that these isolation steps can be avoided by performing the reaction at aqueous conditions. This is more straightforwardly and does not require costly precautions to avoid contact while handling. Moreover, the process of the invention allows to produce the quaternary ammonium salt from a lignocaine compound in a one-pot synthesis involving mostly water.

1 . A process for the preparation of a quaternary ammonium hydroxide R + OH − , in which R +  has the formula: 
     
       
         
         
             
             
         
       
     
     in which R 1  and R 2  each independently represent an alkyl group containing from 1 to 4 carbon atoms and R 3  represents a benzyl group or a substituted benzyl group, said process comprising forming an aqueous solution containing a quaternary ammonium halide having said cation R + , contacting said aqueous solution with hydroxide ions, to obtain a quaternary ammonium hydroxide, and isolating said quaternary ammonium hydroxide. 
   
   
       2 . The process according to  claim 1 , wherein said quaternary ammonium halide is prepared from a lignocaine compound or derivative thereof. 
   
   
       3 . The process according to  claim 1 , wherein said quaternary ammonium halide is a denatonium halide (R 1 , R 2 =ethyl; R 3 =benzyl). 
   
   
       4 . The process according to  claim 1 , wherein said quaternary ammonium hydroxide is denatonium hydroxide (R 1 , R 2 =ethyl; R 3 =benzyl). 
   
   
       5 . A compound, denatonium hydroxide, in its crystalline form, having a melting point between 150 and 160° C. 
   
   
       6 . A process for the preparation of a quaternary ammonium salt having a benzoate, a hydrogen phthalate, a hydrogen tartrate or a hydrogen oxalate anion, or a fatty acid derivative, or their substituted analogues, wherein the process comprises reacting a quaternary ammonium hydroxide isolatable by the process according to  claim 1  with the conjugated acid of said anion or with the fatty acid, in the presence of an organic solvent. 
   
   
       7 . The process according to  claim 6 , wherein the quaternary ammonium salt is denatonium benzoate (R 1 , R 2 =ethyl; R 3 =benzyl) or a denatonium fatty acid derivative (R 1 , R 2 =ethyl; R 3 =fatty acid). 
   
   
       8 . The process according to  claim 2 , wherein said quaternary ammonium halide is a denatonium halide (R 1 , R 2 =ethyl; R 3 =benzyl). 
   
   
       9 . A process for the preparation of a quaternary ammonium salt having a benzoate, a hydrogen phthalate, a hydrogen tartrate or a hydrogen oxalate anion, or a fatty acid derivative, or their substituted analogues, wherein the process comprises reacting a quaternary ammonium hydroxide isolatable by the process according to  claim 2  with the conjugated acid of said anion or with the fatty acid, in the presence of an organic solvent. 
   
   
       10 . A process for the preparation of a quaternary ammonium salt having a benzoate, a hydrogen phthalate, a hydrogen tartrate or a hydrogen oxalate anion, or a fatty acid derivative, or their substituted analogues, wherein the process comprises reacting a quaternary ammonium hydroxide isolatable by the process according to  claim 3  with the conjugated acid of said anion or with the fatty acid, in the presence of an organic solvent. 
   
   
       11 . A process for the preparation of a quaternary ammonium salt having a benzoate, a hydrogen phthalate, a hydrogen tartrate or a hydrogen oxalate anion, or a fatty acid derivative, or their substituted analogues, wherein the process comprises reacting a quaternary ammonium hydroxide isolatable by the process according to  claim 4  with the conjugated acid of said anion or with the fatty acid, in the presence of an organic solvent. 
   
   
       12 . A process for the preparation of a quaternary ammonium salt having a benzoate, a hydrogen phthalate, a hydrogen tartrate or a hydrogen oxalate anion, or a fatty acid derivative, or their substituted analogues, wherein the process comprises reacting a quaternary ammonium hydroxide isolatable by the process according to  claim 8  with the conjugated acid of said anion or with the fatty acid, in the presence of an organic solvent.